ABSTRACT A tremendous amount of progress has been made in identifying the pathways of pathological importance in cancer and in the validation of steps in these pathways as therapeutic targets. However, the genetic heterogeneity among cancers, and the utilization by different tumor types of different growth and survival pathways has made it difficult to realize the therapeutic potential of even the most tractable targets. Addressing this impediment to progress is a central theme of the research being undertaken by members of the Women's Cancer Program where the development of therapeutic strategies that are tailored to specific cancer subtypes is a primary focus. These efforts have led to the identification of targets the inhibition of which are likely to selectively impact triple negative breast cancer, endocrine resistant ER-positive breast cancers, Inflammatory breast cancer, thyroid cancer, and gynecologic cancers. This successful strategy will be continued in the next funding period with efforts being directed towards (a) the definition of pathways of pathological importance in different women's cancers the exploitation of which will yield new strategies for therapeutic intervention, (b) identification and validation of biomarkers which will help to define specific disease characteristics and/or report on the efficacy of treatment regimens, and (c) development of and accrual to innovative clinical trials that build upon the scientific expertise of the program members. These initiatives will be facilitated by the existing infrastructure of the program and by the new opportunities for interaction that are contemplated. The collective experience of 30 primary and 15 secondary program members from across 12 different departments will be brought to bear on these research questions and these initiatives will be supported by a significant portfolio of research grants (~$14M cancer funding/year) that the program has amassed. The Women's Cancer Program is an exceptionally productive and interactive group of scientists having published 706 papers in the past funding period of which 203 were the product of inter-programmatic interactions.